Epigenetics in cancer therapy and nanomedicine

Abstract

The emergence of nanotechnology applied to medicine has revolutionized the treatment of human cancer. As in the case of classic drugs for the treatment of cancer, epigenetic drugs have evolved in terms of their specificity and efficiency, especially because of the possibility of using more effective transport and delivery systems. The use of nanoparticles (NPs) in oncology management offers promising advantages in terms of the efficacy of cancer treatments, but it is still unclear how these NPs may be affecting the epigenome such that safe routine use is ensured. In this work, we summarize the importance of the epigenetic alterations identified in human cancer, which have led to the appearance of biomarkers or epigenetic drugs in precision medicine, and we describe the transport and release systems of the epigenetic drugs that have been developed to date.

Transcription and Translation Inhibitors in Cancer Treatment

“…Changes in the epigenetic landscape are commonly associated with cancer, and thus the enzymes responsible for the epigenetic changes can be inhibited to hinder the disease (Cheng et al, 2019). There are two recent and comprehensive reviews about epigenetic enzyme inhibitors and cancer, and thus this section will include only a short overview of the topic (Cheng et al, 2019;Roberti et al, 2019).…”

Epidrug Repurposing: Discovering New Faces of Old Acquaintances in Cancer Therapy

“…Over time, many definitions of Epigenetics have arisen (13); however, we can understand epigenetics as reversible chemical modifications of DNA and histone proteins (epimarks) that regulate specific functions in chromatin remodeling without altering the DNA sequence (14). Epimarks are associated with the transcription and function of a gene, that may change the cellular phenotype or its functional patterns in response to a particular context, across different developmental stages, cellular differentiation, or maintenance of tissue-specific cell lineages (15).…”

“…Methylation on DNA's cytosine is the most broadly studied epigenetic modification in humans. It encompasses a reaction defined as "the covalent transfer of a methyl group to the C-5 position of a cytosine ring of DNA" (15,19). Generally, in mammals, DNA methylation occurs predominantly-but not exclusively-in the context of genomic regions called CpG islands, which are formed by clusters of CpG dinucleotides, and it's catalyzed by a group of enzymes called DNA methyltransferases (DNMTs).…”

Targeting Epigenetic Dependencies in Solid Tumors: Evolutionary Landscape Beyond Germ Layers Origin

“…There are three different isoforms of DNMT enzymes that show different and non-redundant roles: DNTM1 is critical to maintaining the proper DNA methylation during mitosis, whereas DNMT3A and DNMT3B are more implicated in the methylation process during embryogenesis [16]. Globally, the readout of the DNMTs activity is the hypermethylation of DNA, which is usually associated with the silencing of gene expression [17][18][19]. Aberrant DNMT levels has been detected in many different cancer types through genome-wide analyses, which highlighted a~5-10% increased methylation on CpG islands in cancer specimens compared to normal counterparts, with a consequent silencing of several tumor-suppressor genes (i.e., CDKN2B, RASSF1A, GATA4, CDH1), further supporting the tight correlation between epigenetics abnormalities and cancer initiation and progression [20][21][22][23][24].…”